Circulating human B cells that coexpress V-preB and conventional L chains (V-preB+ L+ B cells) are a recently described subset of B cells that express Abs with features of self-reactivity. Initial analysis of V-preB+ L+ B cells was limited to Ig-κ and to the small, underused V H 5 family. To determine whether Abs commonly expressed by V-preB+ L+ B cells show similar features, we analyzed Ig H chains from three highly expressed V H families, V H 1, V H 3, and V H 4, and Ig-λ. We find that V H 1 and V H 3 Abs expressed by V-preB+ L+ B cells resemble V H 5 in that they display increased J H 6 use, long CDR3s, and an increased frequency of DD fusions. Abs in all three of these V H families also show skewed D reading frame use resulting in predominance of hydrophobic amino acids, which are counterselected in conventional B cells. Like Ig-κ genes, the Ig-λ genes in V-preB+ L+ B cells show long CDR3s, but they differ from Ig-κ genes in that they display no evidence of receptor editing. We conclude that a large number of H and L chain Abs expressed by V-preB+ L+ B cells display features associated with self-reactive Abs.